Over 500,000 worldwide cases of head and neck (H&N) cancer occur annually. Despite aggressive treatment, about 40% of H&N cancers recur and progress. Recent studies of interstitial PDT (I-PDT) have shown promising results in the treatment of patients with locally advanced H&N cancer that fail standard therapies. I-PDT provides a means to treat cancerous tumors while minimizing damage to surrounding tissues and does not exhibit cumulative cell toxicities, distinguishing it from radiation therapy. However, the recent I-PDT studies do not use pre-treatment planning nor treatment monitoring with real time light dosimetry to guide the therapy. As compared to radiation therapy, treatment planning and monitoring for I- PDT remain rudimentary since patient- and tumor-specific photokinetics factors such as tumor oxygenation, photosensitizer (PS) levels and singlet oxygen dose that are critical to the delivery of effective treatment doses are not taken into account. The development of treatment planning and monitoring tools that take into account these factors will fill an unmet clinical need and provide for individualized patient treatment. An effective I-PDT treatment planning and monitoring system is expected to improve therapeutic outcomes, reduce the need for repeat I-PDT or additional cell-killing therapy, and could therefore reduce overall costs in the per patient delivery of cancer-related therapy and care. This SBIR Phase I proposal will be done by Simphotek, Inc. with a subcontract to Roswell Park Cancer Institute (RPCI). The major objective is to develop new prototype software and hardware tools to enable interstitial Intensity-Modulated Photodynamic Therapy (i-IMPDT). The new tools will combine simulations of PS photokinetics with light propagation using fast finite element (FE) analysis techniques that include light scattering and absorption. In the future, these tools will create a platform to provide real time treatment guidance and dose modifications during I-PDT. Simphotek is a world leader in developing sophisticated photokinetics software and RPCI is a world leader in the fields of I-PDT and FE analysis of H&N cancers. This Phase I SBIR has three major aims. Aim 1 is to develop and confirm the accuracy of new customized FE software code and hardware tools to calculate the light dose for I-PDT. To determine simulation accuracy, calculations using the new tools will be compared to phantom measurements done at RPCI mimicking the anatomy of H&N cancer patients. Aim 2 is to adapt Simphotek's photokinetics code to calculate PS fluorescence, PS photobleaching, PS concentration and singlet oxygen dose. Aim 3 is to determine the feasibility of combining the new FE code and the modified photokinetics software code into a unified platform code. After initial development in Phase I, the prototype treatment planning and monitoring tools will be further advanced in Phase II. Clinical trials will be performed in Phase III to determine if the platform code and hardware provides I-PDT physicians and researchers with accurate light dose distributions in cancer tumors and improves patient outcomes.